U.S. patent number 10,537,674 [Application Number 14/881,054] was granted by the patent office on 2020-01-21 for system and method to increase the overall diameter of veins.
This patent grant is currently assigned to Flow Forward Medical, Inc.. The grantee listed for this patent is FLOW FORWARD MEDICAL, INC.. Invention is credited to F. Nicholas Franano.
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United States Patent |
10,537,674 |
Franano |
January 21, 2020 |
System and method to increase the overall diameter of veins
Abstract
A system and method for increasing the speed of blood and wall
shear stress (WSS) in a peripheral vein for a sufficient period of
time to result in a persistent increase in the overall diameter and
lumen diameter of the vein is provided. The method includes pumping
blood at a desired rate and pulsatility. The pumping is monitored
and adjusted, as necessary, to maintain the desired blood speed,
WSS and pulsatility in the peripheral vein in order to optimize the
rate and extent of dilation of the peripheral vein.
Inventors: |
Franano; F. Nicholas (Olathe,
KS) |
Applicant: |
Name |
City |
State |
Country |
Type |
FLOW FORWARD MEDICAL, INC. |
Olathe |
KS |
US |
|
|
Assignee: |
Flow Forward Medical, Inc.
(Olathe, KS)
|
Family
ID: |
44370149 |
Appl.
No.: |
14/881,054 |
Filed: |
October 12, 2015 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20160030648 A1 |
Feb 4, 2016 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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13030054 |
Feb 17, 2011 |
9155827 |
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61305508 |
Feb 17, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M
1/12 (20130101); A61M 1/101 (20130101); A61M
1/1029 (20140204); A61B 17/11 (20130101); A61M
1/14 (20130101); A61M 1/125 (20140204); A61M
1/367 (20130101); A61M 25/0194 (20130101); A61M
1/1008 (20140204); A61M 1/1086 (20130101); A61M
1/10 (20130101); A61B 90/39 (20160201); A61M
1/3655 (20130101); A61M 1/122 (20140204); A61M
2205/0205 (20130101); A61M 2205/3334 (20130101); A61M
2205/8206 (20130101); A61B 2017/1107 (20130101); A61M
2206/10 (20130101); A61B 2090/3966 (20160201) |
Current International
Class: |
A61M
1/36 (20060101); A61M 1/10 (20060101); A61M
25/01 (20060101); A61M 1/14 (20060101); A61B
17/11 (20060101); A61B 90/00 (20160101); A61M
1/12 (20060101) |
References Cited
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2008/136979 |
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Nov 2017 |
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WO |
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Primary Examiner: Zimbouski; Ariana
Attorney, Agent or Firm: Polsinelli
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a divisional of U.S. patent application Ser.
No. 13/030,054, entitled "System and Method to Increase the Overall
Diameter of Veins" filed on Feb. 17, 2011, which issued as U.S.
Pat. No. 9,155,827 on Oct. 13, 2015; which claims priority to U.S.
Provisional Application No. 61/305,508 entitled "System and Method
to Increase the Overall Diameter of Veins" filed on Feb. 17, 2010,
all of which are incorporated herein by reference in their
entireties.
Claims
What is claimed is:
1. A system for persistently increasing an overall diameter and a
lumen diameter of a peripheral vein prior to creation of an
arteriovenous fistula or an arteriovenous graft in a patient,
wherein the system is configured to increase the velocity of blood
in the peripheral vein, the system comprising: a pump-conduit
assembly to remove deoxygenated blood from a donating vein or the
right atrium and pump blood into the peripheral vein, the
pump-conduit assembly including: a pump configured to pump blood,
having a pump inlet and a pump outlet; a first conduit configured
to carry blood, the first conduit having an inlet configured to
fluidly connect to a donating vein or right atrium to remove the
deoxygenated blood from the donating vein or to the right atrium,
such first conduit comprising a first catheter configured for
insertion into a vein and advancement within the lumen of the vein,
including into the right atrium; and an outlet fluidly connected to
the pump inlet; a second conduit configured to carry blood, the
second conduit having an inlet fluidly connected to the pump outlet
and an outlet to fluidly connect to a peripheral vein, the second
conduit comprising a first segment comprising a second catheter and
configured to connect to the pump outlet and a second segment
configured to enable the creation of a surgical anastomosis between
an end of the second segment and the peripheral vein using the end
of the second segment to attach to the side of the peripheral vein;
and a control unit configured to control the pump and pump
deoxygenated blood into the peripheral vein at a rate to maintain a
mean wall shear stress in the peripheral vein between 1.5 Pa and 23
Pa for a period of 7-84 days, wherein the control unit and the
pump-conduit assembly are configured to pump blood in a manner such
that the mean pulse pressure in the conduit fluidly connected to
the peripheral vein is less than 20 mmHg.
2. The system of claim 1, wherein, the first conduit and a first
portion of the second conduit comprises polyvinyl chloride,
polyethylene, polyurethane, or silicone.
3. The system of claim 1, wherein the first conduit is configured
for insertion into the subclavian vein, jugular vein,
brachiocephalic vein, superior vena cava, femoral vein, external
iliac vein, common iliac vein, and inferior vena cava.
4. The system of claim 3, wherein, the first conduit and a first
portion of the second conduit comprises polyvinyl chloride,
polyethylene, polyurethane, or silicone.
5. The system of claim 1, wherein the first conduit or the first
portion of the second conduit comprises an antimicrobial
coating.
6. The system of claim 3, wherein the first conduit or the first
portion of the second conduit comprises an antimicrobial
coating.
7. The system of claim 4, wherein the first conduit or the first
portion of the second conduit comprises an antimicrobial
coating.
8. The system of claim 1, further comprising a cuff that can be
affixed to a portion of the first conduit or the second
conduit.
9. The system of claim 3, further comprising a cuff that can be
affixed to a portion of the first conduit or the second
conduit.
10. The system of claim 4, further comprising a cuff that can be
affixed to a portion of the first conduit or the second
conduit.
11. The system of claim 7, further comprising a cuff that can be
affixed to a portion of the first conduit or the second
conduit.
12. The system of claim 1, wherein the second segment of the second
conduit configured to enable the creation of a surgical anastomosis
between the second segment and the peripheral vein using the end of
the segment to attach to the side of the peripheral vein is
configured to make such surgical anastomosis to the brachial vein,
radial vein, ulnar vein, interosseous vein, femoral vein, profunda
vein, superficial femoral vein, popliteal vein, anterior tibial
vein, posterior tibial vein, or peroneal vein.
13. The system of claim 1, wherein the segment of the second
conduit configured to enable the creation of a surgical anastomosis
between the segment of the second conduit and the peripheral vein
comprises PTFE.
14. The system of claim 12, wherein the segment of the second
conduit configured to enable the creation of a surgical anastomosis
between the segment of the second conduit and the peripheral vein
comprises PTFE.
15. The system of claim 1, wherein the pump of the pump-conduit
assembly is a centrifugal pump.
16. The system of claim 1, wherein the pump of the pump-conduit
assembly is configured to pump blood over an operating range from
50 mL per minute to 1500 mL per minute, or 100 mL per minute to
1000 mL per minute.
17. The system of claim 15, wherein the pump of the pump-conduit
assembly is configured to pump blood over an operating range from
50 mL per minute to 1500 mL per minute, or 100 mL per minute to
1000 mL per minute.
18. The system of claim 1, wherein the pump of the pump-conduit
assembly is driven by an electric motor.
19. The system of claim 1, wherein a combined length of the first
conduit and the second conduit is between 2 cm and 110 cm.
20. The system of claim 1, wherein the pump portion of the
pump-conduit assembly is configured to remain extracorporeal to the
patient.
21. The system of claim 1, wherein the control unit can be manually
adjusted to change the speed of the pump of the pump-conduit
assembly.
22. The system of claim 1, wherein the system is configured to pump
blood at a rate that maintains a mean wall shear stress in the
peripheral vein between 2.5 Pa and 7.5 Pa.
23. The system of claim 1, wherein the system is configured to pump
blood at a rate that maintains a mean blood speed between 15 cm/s
and 100 cm/s in the peripheral vein.
24. The system of claim 1, wherein the system is configured to pump
blood at a rate between 50 ml/min and 1500 ml/min.
25. The system of claim 19, wherein the system is configured to
pump blood at a rate between 50 ml/min and 1500 ml/min.
26. The system of claim 20, wherein the system is configured to
pump blood at a rate between 50 ml/min and 1500 ml/min.
27. The system of claim 1, wherein the pump-conduit assembly and
controller are configured for use in a human patient for a period
of time up to 42 days, such configuration including the use of the
system for a period of time up to 42 days.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to systems and methods for
persistently increasing the overall diameter and the lumen diameter
of veins in patients. Specifically, the present invention relates
to systems and methods that utilize a blood pump to increase the
blood speed and wall shear stress (WSS) on the endothelium of
peripheral veins for a period of time that results in a persistent
increase in the overall diameter and lumen diameter of those
veins.
2. Background Information
Many patients with chronic kidney disease eventually progress to
end-stage renal disease (ESRD) and need renal replacement therapy
in order to remove fluid and waste products from their body and
sustain their life. Most patients with ESRD needing renal
replacement therapy receive hemodialysis. During hemodialysis,
blood is removed from the circulatory system, cleansed in a
hemodialysis machine, and then returned to the circulatory system.
Surgeons create discrete "vascular access sites" that can be used
to remove and return blood rapidly from ESRD patients. While major
advances have been made in the hemodialysis machines themselves and
other parts of the hemodialysis process, the creation of durable
and reliable vascular access sites where blood can be removed and
returned to patients during hemodialysis sessions has seen only
modest improvement and remains the Achilles' heel of renal
replacement therapy. This often results in sickness and death for
ESRD patients and places a large burden on health care providers,
payers, and public assistance programs worldwide.
Hemodialysis access sites generally come in three forms:
arteriovenous fistulas (AVF), arteriovenous grafts (AVG), and
catheters. Each type of site is susceptible to high rates of
failure and complications, as described below.
An AVF is constructed surgically by creating a direct connection
between an artery and vein. A functional wrist AVF is the
longest-lasting, most desirable form of hemodialysis access, with a
mean patency of about 3 years. The vein leading away from the
connection is called the "outflow" vein. Dilation of the outflow
vein is a critical component for an AVF to "mature" and become
usable. It is widely believed that the rapid flow of blood in the
outflow vein created by the AVF and the WSS it exerts on the
endothelium of the vein is the major factor driving vein dilation.
Unfortunately, approximately 80% of patients aren't eligible for
AVF placement in the wrist, usually due to inadequate vein
diameter. For eligible patients where AVF placement is attempted,
the site is not usable without further intervention in about
50%-60% of cases, a problem known as "maturation failure". Small
vessel diameter, especially small vein diameter, has been
identified as an important factor in AVF maturation failure. The
rapid appearance of aggressive vein wall scarring known as "intimal
hyperplasia" has also been identified as an important factor in AVF
maturation failure. It is generally believed that the turbulence
created by the rapid flow of blood out of the artery and into the
vein is a major factor causing this vein wall scarring. Some
investigators also postulate that cyclic stretching of the vein
caused by the entry of pulsatile arterial blood may also play a
role in the stimulation of intimal hyperplasia and outflow vein
obstruction in AVF. As such, there is a teaching that rapid flow is
problematic, and attempts have been made to reduce flow in
hemodialysis access sites by restricting lumen diameter by banding
in order to minimize failure rates. At the current time, no method
exists which preserves positive effects of flow-mediated dilation
while eliminating the negative effects of vein wall scarring and
obstruction. Not surprisingly, a patient newly diagnosed with ESRD
and in need of hemodialysis has only a 50% chance of having a
functional AVF within 6 months after starting hemodialysis. Those
patients without a functional AVF are forced to dialyze with more
costly forms of vascular access and are at a greater risk of
complications, sickness, and death.
The second type of vascular access for hemodialysis is known as an
arteriovenous graft (AVG). An AVG is constructed by placing a
segment of synthetic conduit between an artery and vein, usually in
the arm or leg. A portion of the synthetic conduit is placed
immediately under the skin and used for needle access. More
patients are eligible for AVGs, since veins not visible on the skin
surface can be used for outflow, and the rate of early failure is
much lower than for AVFs. Unfortunately, AVG mean primary patency
is only about 4-6 months, mostly because aggressive intimal
hyperplasia and scarring develops rapidly in the wall of the vein
near the connection with the synthetic conduit, leading to stenosis
and thrombosis. Similar to the situation with AVF failure, the
rapid and turbulent flow of blood created by the AVG is thought to
drive intimal hyperplasia and scarring in the wall of the outflow
vein, often resulting in obstruction of the AVG. Some investigators
also postulate that cyclic stretching of the vein caused by the
entry of pulsatile arterial blood may also play a role in the
formation of intimal hyperplasia and outflow vein obstruction in
AVG. Although AVGs are less desirable than AVFs, about 25% of
patients dialyze with an AVG, mostly because they are not eligible
to receive an AVF.
Patients who are not able to get hemodialysis through an AVF or AVG
must have a large catheter inserted in the neck, chest, or leg in
order to receive hemodialysis. These catheters often become
infected, placing the patient at high risk for sepsis and death.
Patients with catheter sepsis usually require hospitalization,
removal of the catheter, insertion of a temporary catheter,
treatment with IV antibiotics, and then placement of a new catheter
or other type of access site when the infection has cleared.
Catheters are also susceptible to obstruction by thrombus and
fibrin build-up around the tip. Hemodialysis catheters have a mean
patency of about 6 months and are generally the least desirable
form of hemodialysis access. Although catheters are less desirable
than AVFs and AVG, about 20% of patients dialyze with a catheter,
mostly because they have not yet been able to receive a functional
AVF or AVG, or are not eligible to receive an AVF or AVG.
The problem of hemodialysis access site failure has received more
attention recently as the number of ESRD patients undergoing
routine hemodialysis has increased worldwide. In 2004, the Centers
for Medicare & Medicaid Services (CMS) announced a "Fistula
First" initiative to increase the use of AVFs in providing
hemodialysis access for patients with end-stage renal failure. This
major initiative is a response to published Medicare data showing
that patients who dialyze with an AVF have reduced morbidity and
mortality compared to patients with an AVG or a catheter. Costs
associated with AVF patients are substantially lower than the costs
associated with AVG patients in the first year of dialysis, and in
subsequent years. The cost savings of a dialyzing with an AVF are
even greater when compared to dialyzing with a catheter.
To be eligible for an AVF or AVG, patients must have a peripheral
vein with a lumen diameter of at least 2.5 mm or 4 mm,
respectively. However, there is currently no method for
persistently increasing the overall diameter and lumen diameter of
peripheral veins in ESRD patients who are ineligible for an AVF or
AVG due to inadequate vein size. Consequently, patients with veins
that are too small to attempt an AVF or AVG are forced to use less
desirable forms of vascular access such as catheters. Similarly,
there is currently no method of treatment for AVF maturation
failure, which falls disproportionately on patients with small vein
diameters. Thus, systems and methods for enlarging the overall
diameter and lumen diameter of a vein prior to the creation of AVF
or AVG are needed. The importance of this need is highlighted by a
recent study demonstrating that ESRD patients who were forced to
use less desirable forms of vascular access such as catheters had a
substantially higher risk of becoming sick or dying when compared
with patients who were able to use an AVF or AVG for
hemodialysis.
There is also a need to persistently increase vein diameter for
other patients, such as those with atherosclerotic blockage of
peripheral arteries who are in need of peripheral bypass grafting.
Patients with peripheral artery disease (PAD) who have an
obstruction to blood flow in the arteries of the legs often suffer
from claudication, skin ulceration, and tissue ischemia and many of
these patients eventually require amputation of portions of the
affected limb. In some of these patients, the obstruction can be
relieved to an adequate degree by balloon angioplasty or the
implantation of a vascular stent. In many patients, however, the
obstruction is too severe for these types of minimally invasive
therapies. Therefore, surgeons will often create a bypass graft
that diverts blood around the obstructed arteries and restores
adequate blood flow to the affected extremity. However, many
patients in need of a peripheral bypass graft cannot use their own
veins as bypass conduits due to inadequate vein diameter and are
forced to use synthetic conduits made of materials such as
polytetrafluoroethylene (PTFE, e.g. Gore-Tex) or polyethylene
terephthalate (PET, e.g. Dacron). Studies have shown that using a
patient's own veins as bypass conduits results in better long term
patency than using synthetic bypass conduits made from materials
such as PTFE or Dacron. The use of a synthetic bypass conduit
increases the risk of stenosis in the artery at the distal end of
the graft and thrombosis of the entire conduit, resulting in bypass
graft failure and a recurrence or worsening of symptoms. Thus,
systems and methods for increasing the overall diameter and lumen
diameter of veins prior to the creation of bypass grafts are
needed, especially for patients who are ineligible to use their own
veins for the creation of a bypass graft due to inadequate vein
diameter.
In view of the above, it will be apparent to those skilled in the
art from this disclosure that there exists a need for a system and
method for persistently increasing the lumen diameter and overall
diameter of peripheral veins so that those veins can be used for
the creation of hemodialysis access sites and bypass grafts. The
invention described herein addresses this need in the art as well
as other needs, which will become apparent to those skilled in the
art from this disclosure.
SUMMARY OF THE INVENTION
The present invention includes methods of using a blood pump to
increase the overall diameter and the lumen diameter of peripheral
veins. Systems and methods are described wherein the wall shear
stress (WSS) exerted on the endothelium of the peripheral vein is
increased by placing a blood pump upstream of the peripheral vein
for a period of time sufficient to result in dilation of the
peripheral vein. The pump directs the blood into the peripheral
vein preferably in a manner wherein the blood has reduced pulse
pressure when compared with the pulse pressure of blood in a
peripheral artery.
Studies have shown hemodynamic forces and changes in hemodynamic
forces within veins play a vital role in determining the overall
diameter and lumen diameter of those veins. For example, persistent
increases in blood speed and WSS can lead to vein dilation, with
the amount of dilation being dependent both on the level of
increased blood speed and WSS and the time that the blood speed and
WSS are elevated. The elevated blood speed and WSS are sensed by
endothelial cells, which trigger signaling mechanisms that result
in stimulation of vascular smooth muscle cells, attraction of
monocytes and macrophages, and synthesis and release of proteases
capable of degrading components of the extracellular matrix such as
collagen and elastin. As such, the present invention relates to
increasing blood speed and WSS for a period of time sufficient to
result in vein remodeling and dilation, preferably for a period of
time greater than seven days. The present invention also relates to
methods of periodic adjustment of pump parameters to optimize vein
remodeling and dilation.
Wall shear stress has been shown to be the key factor for blood
vessel dilation in response to an increased blood flow. Assuming a
Hagen-Poiseuille blood flow in the vessel (i.e. a laminar flow with
a fully developed parabolic velocity profile), then WSS is given by
the equation: WSS(.tau.)=4Q.mu./.pi.R3, where:
Q=volume flow rate in mL/s
.mu.=viscosity of blood in units of poise
R=radius of vessel in cm
.tau.=wall shear stress in dynes/cm2
The systems and methods described herein increase the WSS level in
a peripheral vein. Normal WSS for veins ranges between 0.076 Pa and
0.76 Pa. The systems and methods described herein increase the WSS
level to a range between 0.76 Pa and 23 Pa, preferably to a range
between 2.5 Pa and 7.5 Pa. Preferably, the WSS is increased for
between 7 days and 84 days, or preferably between 7 and 42 days, to
induce persistent dilation in the peripheral accepting vein such
that veins that were initially ineligible for use as a hemodialysis
access site or bypass graft due to a small vein diameter become
usable. This can also be accomplished by intermittently increasing
WSS during the treatment period, with intervening periods of normal
WSS.
The systems and methods described herein also increase the speed of
blood in peripheral veins and in certain instances, peripheral
arteries. At rest, the mean speed of blood in the cephalic vein in
humans is generally between 5-9 cm/s, while the speed of blood in
the brachial artery is generally between 10-15 cm/s. For the
systems and methods described herein, the mean speed of blood in
the peripheral vein is increased to a range between 15 cm/s-100
cm/s, preferably to a range between 25 cm/s and 100 cm/s, depending
on the diameter of peripheral accepting vein and the length of time
the pumping of blood into the peripheral accepting vein is planned.
Preferably, the mean blood speed is increased for between 7 days
and 84 days, or preferably between 7 and 42 days, to induce
persistent dilation in the peripheral accepting vein such that
veins that were initially ineligible for use as a hemodialysis
access site or bypass graft due to a small vein diameter become
usable. This can also be accomplished by intermittently increasing
mean blood speed during the treatment period, with intervening
periods of normal mean blood speed.
A method of increasing the lumen diameter and overall diameter of a
peripheral vein in a patient is set forth herein. The method
comprises performing a first procedure to access an artery or vein
(the donating vessel) and a peripheral vein (the accepting vein)
and connecting the donating vessel to the accepting vein with a
pump system. The pump system is then activated to artificially
direct blood from the donating vessel to the accepting vein. The
method also includes monitoring the blood pumping process for a
period of time. The method further includes adjusting the speed of
the pump, the speed of the blood being pumped, or the WSS on the
endothelium of the accepting vein and monitoring the pumping
process again. After a period of time has elapsed to allow for vein
dilation, the diameter of the accepting vein is measured to
determine if adequate persistent increase in the overall diameter
and lumen diameter of the accepting vein has been achieved and the
pumping process is adjusted again, as necessary, When adequate
amount of persistent increase in the overall diameter and lumen
diameter of the accepting vein has been achieved, a second surgery
is performed to remove the pump. A hemodialysis access site (such
as an AVF or AVG) or bypass graft can be created at this time, or a
later time, using at least a portion of the persistently enlarged
accepting vein.
In one embodiment, a surgical procedure is performed to expose
segments of two veins. One end of a first synthetic conduit is
"fluidly" connected (i.e. joined lumen to lumen to permit fluid
communication therebetween) to the vein where blood is to be
removed (the donating vein). The other end of the first synthetic
conduit is fluidly connected to the inflow port of a pump. One end
of a second synthetic conduit is fluidly connected to the vein
where blood is to be directed (the accepting vein). The other end
of the second synthetic conduit is fluidly connected to the outflow
port of the same pump. Deoxygenated blood is pumped from the
donating vein to the accepting vein until the vein has persistently
dilated to the desired overall diameter and lumen diameter. The
term "persistently dilated" is used herein to mean that even if a
pump is turned off an increase in overall diameter or lumen
diameter of a vessel can still be demonstrated, when compared to
the diameter of the vein prior to the period of blood pumping. That
is, the vessel has become larger independent of the pressure
generated by the pump. Once the desired amount of persistent vein
enlargement has occurred, a second surgical procedure is performed
to remove the pump and synthetic conduits. A hemodialysis access
site (such as an AVF or AVG) or bypass graft can be created at this
time, or a later time, using at least a portion of the persistently
enlarged accepting vein. In this embodiment, the pump port may be
fluidly connected directly to the donating vein or the accepting
vein without using an interposed synthetic conduit. In a variation
of this embodiment, the accepting vein may be located in one body
location, such as the cephalic vein in an arm and the donating vein
may be in another location, such as the femoral vein in a leg. In
this instance, the two ends of the pump-conduit assembly will be
located within the body and a bridging portion of the pump-conduit
assembly may be extracorporeal (outside the body, e.g. worn under
the clothing) or intracorporeal (inside the body, e.g. tunneled
under the skin) Furthermore, in certain instances, the donating
vessel may be more peripheral in relative body location than the
accepting vein.
In another embodiment, a method comprises a surgical procedure that
is performed to expose a segment of a peripheral artery and a
segment of a peripheral vein. One end of a first synthetic conduit
is fluidly connected to the peripheral artery. The other end of the
first synthetic conduit is fluidly connected to the inflow port of
a pump. One end of a second synthetic conduit is fluidly connected
to the peripheral vein. The other end of the second synthetic
conduit is fluidly connected to the outflow port of the same pump.
Pumping oxygenated blood from the peripheral artery to the
peripheral vein is performed until the vein has persistently
dilated to the desired overall diameter and lumen diameter. Once
the desired amount of vein enlargement has occurred, a second
surgical procedure is performed to remove the pump and synthetic
conduits. A hemodialysis access site (such as an AVF or AVG) or
bypass graft can be created at this time, or a later time, using at
least a portion of the persistently enlarged accepting vein. A
variation of this embodiment is provided wherein the pump port may
be fluidly connected directly to the artery or vein without using
an interposed synthetic conduit.
In yet another embodiment, a pair of specialized catheters are
inserted into the venous system. The first end of one catheter is
attached to the inflow port of a pump (hereafter the "inflow
catheter") while the first end of the other catheter is attached to
the outflow port of the pump (hereafter the "outflow catheter").
Optionally, the two catheters can be joined together, such as with
a double lumen catheter. The catheters are configured for insertion
into the lumen of the venous system. After insertion, the tip of
the second end of the inflow catheter is positioned in anywhere in
the venous system where a sufficient amount of blood can be drawn
into the inflow catheter (e.g. the right atrium, superior vena
cava, subclavian vein, or brachiocephalic vein). After insertion,
the tip of the second end of the outflow catheter is positioned in
a segment of peripheral vein (the accepting vein) in the venous
system where blood can be delivered by the outflow catheter (e.g.
cephalic vein). The pump then draws deoxygenated blood into the
lumen of the inflow catheter from the donating vein and discharges
the blood from the outflow catheter and into the lumen of the
accepting vein. In this embodiment, the pump and a portion of the
inflow catheter and outflow catheters remain external to the
patient. The pump is operated until the desired amount of
persistent overall diameter and lumen diameter enlargement has
occurred in the accepting vein, whereupon the pump and catheters
are removed. A hemodialysis access site (such as an AVF or AVG) or
bypass graft can be created at this time, or a later time, using at
least a portion of the persistently enlarged accepting vein.
A system for increasing the blood speed and WSS in a vein by
delivery of deoxygenated blood from a donating vein to an accepting
vein in a patient is provided that comprises two synthetic
conduits, each with two ends, a blood pump, a control unit, and a
power source. This system may also contain one or more sensor
units. In one embodiment of the system, the synthetic conduits and
pump, collectively known as the "pump-conduit assembly" is
configured to draw deoxygenated blood from the donating vein or the
right atrium and pump that blood into the accepting vein. The
pump-conduit assembly is configured to pump deoxygenated blood. In
another embodiment of the system, the pump-conduit assembly is
configured to draw oxygenated blood from a peripheral artery and
pump the blood into a peripheral vein. The blood is pumped in a
manner that increases the blood speed in the artery and vein and
increases WSS exerted on the endothelium of the artery and vein for
a period of time sufficient to cause a persistent increase in the
overall diameter and lumen diameter of the peripheral artery and
vein. Preferably, the blood being pumped into peripheral vein has
low pulsatility, for example lower pulsatility than the blood in a
peripheral artery. A variation of this embodiment is provided
whereby the pump is fluidly connected directly to the artery or
vein (or both) without using an interposed synthetic conduit. The
pump includes an inlet and an outlet, and the pump is configured to
deliver deoxygenated or oxygenated blood to the peripheral vein in
a manner that increases the speed of the blood in the vein and the
WSS exerted on the endothelium in the vein to cause a persistent
increase in the overall diameter and the lumen diameter of the
peripheral vein. The blood pump may be implanted in the patient,
may remain external to the patient, or may have implanted and
external portions. All or some of the synthetic conduits may be
implanted in the patient, may be implanted subcutaneously, or may
be implanted within the lumen of the venous system, or any
combination thereof. The implanted portions of pump-conduit
assembly may be monitored and adjusted periodically, for example,
every seven days.
The invention includes methods of increasing the blood speed in a
peripheral vein and increasing the WSS exerted on the endothelium
of a peripheral vein of a human patient in need of a hemodialysis
access site or a bypass graft are also provided. A device designed
to augment arterial blood flow for the treatment of heart failure
would be useful for this purpose. Specifically, a ventricular
assist device (VAD) which is optimized for low blood flows would be
capable of pumping blood from a donating vessel to a peripheral
vein to induce a persistent increase in overall diameter and lumen
diameter of the peripheral vein. In various embodiments, a
pediatric VAD, or a miniature VAD designed to treat moderate heart
failure in adults (such as the Synergy pump by Circulite) may be
used. Other devices, including an LVAD or an RVAD that are
optimized for low blood flows, may also be used.
The method comprises fluidly connecting the low-flow VAD, a
derivative thereof, or a similar type device to a donating vessel,
drawing blood from the donating vessel, and pumping it into the
peripheral accepting vein for a sufficient amount of time to cause
a desired amount of persistent increase in the overall diameter and
the lumen diameter of the peripheral vein. The blood pump may be
implanted into the patient or it may remain external to the
patient. When the pump is external to the patient, it may be
affixed to the patient for continuous pumping. Alternatively, the
pump may be configured to detach from the donating and accepting
vessels of the patient for periodic and/or intermittent pumping
sessions.
The lumen diameter of peripheral accepting veins can be monitored
while the blood is being pumped into the vein using conventional
methods such as visualization with ultrasound or diagnostic
angiography. A pump-conduit assembly or pump-catheter assembly may
incorporate features that facilitate diagnostic angiography such as
radiopaque markers that identify sites that can be accessed with
needle for injection of contrast into the assembly that will
subsequently flow into the accepting peripheral vein and make it
visible during fluoroscopy using both conventional and digital
subtraction angiography.
When a portion of a pump-conduit assembly or pump catheter assembly
is located external to the body, then an antimicrobial coating or
cuff may be affixed to the portion of the device that connects the
implanted and external components. For example, when a controller
and/or power source is strapped to the wrist, attached to a belt,
or carried in a bag or pack, then the antimicrobial coating is
placed on or around a connection and/or entry point where the
device enters the patient's body.
These and other objects, features, aspects and advantages of the
present invention will become apparent to those skilled in the art
from the following detailed description, which, taken in
conjunction with the annexed drawings, discloses preferred
embodiments of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Referring now to the attached drawings which form a part of this
original disclosure:
FIG. 1A is a schematic view of a pump-conduit assembly of a system
and method in accordance with a first embodiment of the present
invention;
FIG. 1B is a schematic view of the pump-conduit assembly of FIG. 1A
as applied to a circulatory system of a patient in accordance with
the first embodiment of the present invention;
FIG. 1C is a magnified view of a portion of FIG. 1B;
FIG. 2A is a schematic view of a pump-conduit assembly of a system
and method in accordance with a second embodiment of the present
invention;
FIG. 2B is a schematic view of the pump-conduit assembly of FIG. 2A
as applied to a circulatory system of a patient in accordance with
the second embodiment of the present invention;
FIG. 2C is a magnified view of a portion of FIG. 2B;
FIG. 3 is a schematic view of a pump-conduit assembly of a system
and method as applied to a circulatory system of a patient in
accordance with a third embodiment of the present invention;
FIG. 4A is a schematic view of a pump-catheter assembly of a system
and method in accordance with a fourth embodiment of the present
invention;
FIG. 4B is a schematic view of the pump-catheter assembly of FIG.
4A as applied to a circulatory system of a patient in accordance
with the fourth embodiment of the present invention;
FIG. 5A is a schematic view of a pump-conduit assembly of a system
and method in accordance with a fifth embodiment of the present
invention;
FIG. 5B is a schematic view of the pump-conduit assembly of FIG. 5A
as applied to a circulatory system of a patient in accordance with
the fifth embodiment of the present invention;
FIG. 6 is a schematic diagram of a pump operated in conjunction
with a control unit for use in any of the above-mentioned
embodiments;
FIG. 7 is a flow chart of a method in accordance with the first and
third embodiments of the present invention;
FIG. 8 is a flow chart of a method in accordance with the second
and fourth embodiments of the present invention; and
FIG. 9 is a flow chart of a method in accordance with the fifth
embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Preferred embodiments of the present invention will now be
explained with reference to the drawings. It will be apparent to
those skilled in the art from this disclosure that the following
description of the embodiments of the present invention is provided
for illustration only and not for limiting the invention as defined
by the appended claims and their equivalents. Referring initially
to FIGS. 1-4, a system 10 to increase the overall diameter of veins
is illustrated as used for a patient 20. The system 10 removes
deoxygenated venous blood from the patient's venous system 22 and
redirects that blood into the accepting peripheral vein 30. The
system 10 also increases the speed of blood in the accepting
peripheral vein 30 and increases the WSS exerted on the endothelium
of the accepting peripheral vein 30, to increase the diameter of
the accepting peripheral vein 30 located, for example, in an arm 24
or a leg 26. The diameter of blood vessels such as peripheral veins
can be determined by measuring the diameter of the lumen, which is
the open space at the center of blood vessel where blood is
flowing. For the purpose of this application, this measurement is
referred to as "lumen diameter". The diameter of blood vessels can
be determined by measuring the diameter in a manner that includes
the wall of the blood vessel. For the purpose of this application,
this measurement is referred to as "overall diameter". The
invention relates to simultaneously and persistently increasing the
overall diameter and lumen diameter of a peripheral vein by
directing blood (preferably with low pulsatility) into the
peripheral vein, thereby increasing the speed of the blood in the
peripheral vein and increasing the WSS on the endothelium of the
peripheral vein. Systems and methods are described wherein the
speed of the blood in a peripheral vein and the WSS on the
endothelium of the peripheral vein is increased by using a pump.
Preferably, the pump directs blood into the peripheral vein,
wherein the pumped blood has reduced pulsatility, such as when the
pulse pressure is lower than blood in a peripheral artery.
The systems and methods described herein increase the WSS level in
a peripheral vein. Normal WSS for veins ranges between 0.076 Pa and
0.76 Pa. The systems and methods described herein are configured to
increase the WSS level in the accepting peripheral vein to range
from about 0.76 Pa and 23 Pa, preferably to a range between 2.5 Pa
and 7.5 Pa. Sustained WSS less than 0.76 Pa might dilate veins but
at a rate that is comparatively slow. Sustained WSS greater than 23
Pa are likely to cause denudation (loss) of the endothelium of the
vein, which is known to retard dilation of blood vessels in
response to increases in blood speed and WSS. Pumping blood in a
manner that increases WSS to the desired range for preferably at
least 7 days, and more preferably between about 14 and 84 days, for
example, produces an amount of persistent dilation in the accepting
peripheral vein such that veins that were initially ineligible for
use as a hemodialysis access site or bypass graft due to small vein
diameter become usable. The blood pumping process may be monitored
and adjusted periodically. For example, the pump may be adjusted
every seven days to account for changes in the peripheral vein
prior to achieving the desired persistent dilation.
The systems and methods described herein also increase the speed of
blood in peripheral veins and in certain instances, peripheral
arteries. At rest, the mean speed of blood in the cephalic vein in
humans is generally between 5-9 cm/s, while the speed of blood in
the brachial artery is generally between 10-15 cm/s. For the
systems and methods described herein, the mean speed of blood in
the peripheral vein is increased to a range between 15 cm/s-100
cm/s, preferably to a range between 25 cm/s and 100 cm/s, depending
on the diameter of peripheral accepting vein and the length of time
the pumping of blood into the peripheral accepting vein is planned.
Preferably, the mean blood speed is increased for between 7 days
and 84 days, or preferably between 7 and 42 days, to induce
persistent dilation in the peripheral accepting vein such that
veins that were initially ineligible for use as a hemodialysis
access site or bypass graft due to a small vein diameter become
usable. This can also be accomplished by intermittently increasing
mean blood speed during the treatment period, with intervening
periods of normal mean blood speed.
Studies have shown hemodynamic forces and changes in hemodynamic
forces within veins play a vital role in determining the overall
diameter and lumen diameter of those veins. For example, persistent
increases in blood speed and WSS can lead to vein dilation. The
elevated blood speed and WSS are sensed by endothelial cells, which
trigger signaling mechanisms that result in stimulation of vascular
smooth muscle cells, attraction of monocytes and macrophages, and
synthesis and release of proteases capable of degrading components
of the extracellular matrix such as collagen and elastin. As such,
the present invention relates to increasing blood speed and WSS for
a period of time sufficient to result in vein remodeling and
dilation.
Assuming a Hagen-Poiseuille blood flow in the vessel (i.e. a
laminar flow with a fully developed parabolic velocity profile),
then WSS can be determined using the equation:
WSS(.tau.)=4Q.mu./.pi.R.sup.3, where:
Q=volume flow rate in mL/s
.mu.=viscosity of blood in units of poise
R=radius of vessel in cm
.tau.=wall shear stress in dynes/cm2
The systems and methods described herein increase the WSS level in
a peripheral vein. Normal WSS for veins ranges between 0.076 Pa and
0.76 Pa. The systems and methods described herein increase the WSS
level to a range between 0.76 Pa and 23 Pa, preferably to a range
between 2.5 Pa and 7.5 Pa. Preferably, the WSS is increased for
between 7 days and 84 days, or preferably between 7 and 42 days, to
induce persistent dilation in the peripheral accepting vein such
that veins that were initially ineligible for use as a hemodialysis
access site or bypass graft due to a small vein diameter become
usable. This can also be accomplished by intermittently increasing
WSS during the treatment period, with intervening periods of normal
WSS.
WSS levels in the accepting peripheral vein lower than 0.076 Pa may
dilate veins however, this would likely occurs at a slow rate. WSS
levels in accepting peripheral veins higher than about 23 Pa are
likely to cause denudation (loss) of the endothelium of the veins.
Denudation of the endothelium of blood vessels is known to retard
dilation in the setting of increased in blood speed and WSS. The
increased WSS induces sufficient persistent dilation in the veins,
such that those that were initially ineligible for use as a
hemodialysis access site or bypass graft due to a small diameter
become usable. The diameter of the accepting vein can be determined
intermittently, such as every 7-14 days for example, to allow for
pump speed adjustment in order to optimize vein dilation during the
treatment period.
The systems and methods described herein also increase the speed of
blood in peripheral veins and in certain instances, peripheral
arteries. At rest, the mean speed of blood in the cephalic vein in
humans is generally between 5-9 cm/s, while the speed of blood in
the brachial artery is generally between 10-15 cm/s. For the
systems and methods described herein, the mean speed of blood in
the peripheral vein is increased to a range between 15 cm/s-100
cm/s, preferably to a range between 25 cm/s and 100 cm/s, depending
on the diameter of peripheral accepting vein and the length of time
the pumping of blood into the peripheral accepting vein is planned.
Preferably, the mean blood speed is increased for between 7 days
and 84 days, or preferably between 7 and 42 days, to induce
persistent dilation in the peripheral accepting vein such that
veins that were initially ineligible for use as a hemodialysis
access site or bypass graft due to a small vein diameter become
usable. Mean blood speed levels in the accepting peripheral vein
lower than 15 cm/s may dilate veins however, this would likely
occurs at a slow rate. Mean blood velocity levels in accepting
peripheral veins higher than about 100 cm/s are likely to cause
denudation (loss) of the endothelium of the veins. Denudation of
the endothelium of blood vessels is known to retard dilation in the
setting of increased in blood speed. The increased mean blood speed
induces sufficient persistent dilation in the veins, such that
those that were initially ineligible for use as a hemodialysis
access site or bypass graft due to a small diameter become usable.
The diameter of the accepting vein can be determined
intermittently, such as every 7-14 days for example, to allow for
pump speed adjustment in order to optimize vein dilation during the
treatment period.
Referring to FIGS. 1-3, the system 10 includes a pump-conduit
assembly 12 for directing deoxygenated venous blood from a donating
vein 29 of the venous system 22 of the patient 20 to the peripheral
or accepting vein 30. In various embodiments, the peripheral or
accepting vein 30 may be a cephalic vein, radial vein, median vein,
ulnar vein, antecubital vein, median cephalic vein, median basilic
vein, basilic vein, brachial vein, lesser saphenous vein, greater
saphenous vein, or femoral vein. Other veins that might be useful
in the creation of a hemodialysis access site or bypass graft or
other veins useful for other vascular surgery procedures requiring
the use of veins may be used. The pump-conduit assembly 12 delivers
the deoxygenated blood to the peripheral or accepting vein 30. The
rapid speed of the blood 34 and the elevated WSS in the peripheral
vein 30 causes the peripheral or accepting vein 30 to enlarge over
time. Thus, the system 10 and method 100 (referring to FIGS. 7-9)
of the present invention advantageously increases the diameter of
the peripheral or accepting vein 30 so that it can be used, for
example, to construct an AVF or AVG access site for hemodialysis or
as a bypass graft.
As used herein, deoxygenated blood is blood that has passed through
the capillary system and had oxygen removed by the surrounding
tissues and then passed into the venous system 22. A peripheral
vein 30, as used herein, means any vein with a portion residing
outside of the chest, abdomen, or pelvis. In the embodiment shown
in FIGS. 1A and 2A, the peripheral or accepting vein 30 is the
cephalic vein. However, in other embodiments, the peripheral vein
30 may be a radial vein, median vein, ulnar vein, antecubital vein,
median cephalic vein, median basilic vein, basilic vein, brachial
vein, lesser saphenous vein, greater saphenous vein, or femoral
vein. In addition to a peripheral vein, other veins that might be
useful in the creation of a hemodialysis access site or bypass
graft or other veins useful for other vascular surgery procedures
requiring the use of veins may also be used, such as those residing
in the chest, abdomen, and pelvis.
In order to reduce pulsatility and/or provided low-pulsatile flow,
a number of pulsatility dampening techniques may be used. By way of
example, and not limitation, such techniques include tuning the
head-flow characteristics of a blood pump, adding compliance to the
pump outflow, and/or modulating the pump speed.
An AVF created using the cephalic vein at the wrist is a preferred
form of vascular access for hemodialysis but this vein is
frequently of inadequate diameter to facilitate the creation of an
AVF in this location. Thus, the present invention is most
advantageous to creating wrist AVFs in ESRD patients and increasing
the percentage of ESRD patients that receive hemodialysis using a
wrist AVF as a vascular access site.
The pump-conduit assembly 12 includes a blood pump 14 and synthetic
conduits 16 and 18, i.e. an inflow conduit 16 and an outflow
conduit 18. Blood pumps have been developed as a component of
ventricular assist devices (VADs) and have been miniaturized to
treat both adult patients with moderate heart failure and pediatric
patients. These pumps can be implanted or remain external to the
patient and are usually connected to a controller and a power
source. Referring to FIG. 6, a schematic diagram of the
pump-conduit assembly 12 is illustrated. The pump 14 can be a
rotary pump such as an axial, mixed flow, or centrifugal pump.
Without recognizing specific limitations, the bearing for the pump
14 can be constructed with magnetic fields, with hydrodynamic
forces, or using a mechanical contact bearing such as a double-pin
bearing. Pumps used in pediatric VAD systems or other low flow VAD
systems can be used. Alternatively, the pump 14 can be an
extracardiac pump such as that shown and described in U.S. Pat.
Nos. 6,015,272 and 6,244,835, both of which are hereby incorporated
herein by reference. These pumps are suitable for use in the system
10 and method 100 of the present invention. The pump 14 has an
inlet 38 to receive deoxygenated blood drawn through the inflow
conduit 16 and an outlet 40 for blood flow 34 to exit the pump 14.
In regards to pumps used in pediatric VAD systems or other low flow
VAD systems suitable for use as pump 14 of the present invention,
these pumps can be sized as small as about the size of a AA battery
or the diameter of a United States half dollar or quarter, and can
weigh as little as about 25-35 g or less. These pumps are designed
to pump about 0.3 to 1.5 L/min or 1 to 2.5 L/min, for example.
Modifications to these pumps could be made to reduce this range to
as low as 0.05 L/min for use in small diameter veins. A priming
volume can be about 0.5-0.6 ml, for example. The blood-contacting
surfaces of the pump 14 preferably include Ti6Al4V and commercially
pure titanium alloys and can include other materials such as
injection-moldable ceramics and polymers, and alternative titanium
alloys, e.g. Ti6Al7Nb. The blood-contacting surface also preferably
has one or more coatings and surface treatments. As such, any of a
variety of pumping devices can be used so long as it can be
connected to the vascular system and can pump a sufficient amount
of blood such that the desired WSS is achieved in the accepting
vein.
The pump 14 includes various components 42 and a motor 44, as shown
in FIG. 6. The various components 42 and motor 44 can be those
common to a VAD. For example, the components 42 include one or more
of a shaft, impeller blades, bearings, stator vanes, rotor, or
stator. The rotor can be magnetically levitated. The motor 44 can
include a stator, rotor, coil, and magnets. The motor 44 may be any
suitable electric motor, such as a multi-phase motor controlled via
pulse-width modulated current.
The system 10 and method 100 can utilize one or more of the pumps
described in the following publications: The PediaFlow.TM.
Pediatric Ventricular Assist Device, P. Wearden, et al., Pediatric
Cardiac Surgery Annual, pp. 92-98, 2006; J. Wu et al., Designing
with Heart, ANSYS Advantage, Vol. 1, Iss. 2, pp. s12-s13, 2007; and
J. Baldwin, et al., The National Heart, Lung, and Blood Institute
Pediatric Circulatory Support Program, Circulation, Vol. 113, pp.
147-155, 2006. Other examples of pumps that can be used as the pump
14 include: the Novacor, PediaFlow, Levacor, or MiVAD from World
Heart, Inc.; the Debakey Heart Assist 1-5 from Micromed, Inc.; the
HeartMate XVE, HeartMate II, HeartMate III, IVAD, or PVAD from
Thoratec, Inc.; the Impella, BVS5000, AB5000, or Symphony from
Abiomed, Inc.; the TandemHeart from CardiacAssist, Inc.; the
VentrAssist from Ventracor, Inc.; the Incor or Excor from Berlin
Heart, GmbH; the Duraheart from Terumo, Inc.; the HVAD or MVAD from
HeartWare, Inc.; the Jarvik 2000 Flowmaker or Pediatric Jarvik 2000
Flowmaker from Jarvik Heart, Inc.; the Gyro C1E3 from Kyocera,
Inc.; the CorAide or PediPump from the Cleveland Clinic Foundation;
the MEDOS HIA VAD from MEDOS Medizintechnik AG; the pCAS from
Ension, Inc; the Synergy from Circulite, Inc; the CentriMag,
PediMag, and UltraMag from Levitronix, LLC; and, the BP-50 and
BP-80 from Medtronic, Inc. The pumps can be monitored and adjusted
manually or with a software program, application, or other
automated system. The software program can automatically adjust the
pump speed to maintain the desired amount of blood flow and WSS in
the accepting vein. Alternatively, the vein diameter and blood flow
may be periodically checked manually and the pump may be manually
adjusted, for example, by tuning the head-flow characteristics of
the pump, adding compliance to the pump outflow, and/or modulating
the pump speed. Other adjustments may also be made.
The synthetic conduits 16 and 18 are comprised of PTFE and/or
Dacron, preferentially reinforced so that the synthetic conduits 16
and 18 are less susceptible to kinking and obstruction. All or a
portion of the conduits 16 and 18 may be comprised of materials
commonly used to make hemodialysis catheters such as polyvinyl
chloride, polyethylene, polyurethane, and/or silicone. The
synthetic conduits 16 and 18 can be of any material or combination
of materials so long as the conduits 16 and 18 exhibit necessary
characteristics, such as flexibility, sterility, resistance to
kinking, and can be connected to a blood vessel via an anastomosis
or inserted into the lumen of a blood vessel, as needed. In
addition, the synthetic conduits 16 and 18 preferably exhibit the
characteristics needed for tunneling (as necessary) and have
luminal surfaces that are resistant to thrombosis. As another
example, the synthetic conduits 16 and 18 can have an exterior
layer composed of a different material than the luminal layer. The
synthetic conduits 16 and 18 can also be coated with silicon to aid
in removal from the body and avoid latex allergies. In certain
embodiments, the connection between the synthetic conduit 16 or 18
and the vein 29 or 30 is made using a conventional surgical
anastomosis, using suture in a running or divided fashion,
henceforth described as an "anastomotic connection." An anastomotic
connection can also be made with surgical clips and other standard
ways of making an anastomosis.
Referring to FIGS. 1-3, the synthetic inflow conduit 16 has a first
end 46 configured to fluidly connect to a donating vein 29 or the
right atrium 31 of the heart and a second end 48 connected to the
inlet 38 of the pump 14. The donating vein 29 can include an
antecubital vein, basilic vein, brachial vein, axillary vein,
subclavian vein, jugular vein, brachiocephalic vein, superior vena
cava, lesser saphenous vein, greater saphenous vein, femoral vein,
common iliac vein, external iliac vein, superior vena cava,
inferior vena cava, or other veins capable of providing sufficient
blood flow to the pump for the purpose of causing persistent
dilation of the accepting peripheral vein. The synthetic outflow
conduit 18 has a first end 52 configured to fluidly connect to the
peripheral accepting vein 30 and a second end 54 connected to the
outlet 40 of the pump 14. The pump-conduit assembly 12 is
configured to redirect blood from the donating vein 29 to the
peripheral accepting vein 30 in a manner that increases the blood
speed and WSS in the peripheral vein to the desired level for a
period of time sufficient to cause a persistent increase in the
overall diameter and lumen diameter of the peripheral vein. In
certain embodiments, a portion of the synthetic conduits 16, 18 may
be extracorporeal to the patient 20. Referring to FIGS. 1 and 3,
the first end 46 of the inflow conduit 16 and the first end 52 of
the outflow conduit 18 are configured for an anastomotic
connection. As shown in FIGS. 1B and 1C, the first end 46 is
fluidly connected to the internal jugular vein (which serves as the
donating vein 29) via an anastomotic connection and the first end
52 of the outflow conduit 18 is fluidly connected to the cephalic
vein (which serves as the peripheral accepting vein 30) via an
anastomotic connection.
Referring to FIGS. 2A-2C, the first end 46 of the synthetic inflow
conduit 16 is configured as a catheter. The fluid connection
between the synthetic inflow conduit 16 and the venous system is
made by positioning the tip of the catheter portion 50 of the
synthetic inflow conduit into the superior vena cava 27, henceforth
described as a "catheter connection". When a catheter connection is
made with a donating vein 29 (in this case, the superior vena cava
27), the catheter portion 50 of the synthetic inflow conduit 46 may
enter the venous system at any location where the vein lumen
diameter is adequate to accept the catheter portion 50. The tip of
the catheter portion 50 may be placed at any location where
sufficient blood can be drawn into the catheter to provide the
desired blood flow 34 to the accepting vein 30. Preferred locations
for the tip of the catheter portion 50 include, but are not limited
to a brachiocephalic vein, the superior vena cava 27, and the right
atrium 31. In the embodiment illustrated in FIGS. 2B-2C, the system
10 draws deoxygenated blood from the superior vena cava 27 of the
patient 20 and redirects it to the cephalic vein 30 in the arm
24.
In another embodiment shown in FIG. 3, the system 10 redirects
deoxygenated venous blood from donating vein 29 (in this case, the
more central portion of the greater saphenous vein) to the
peripheral accepting vein 30 (in this case, a more peripheral
portion of the greater saphenous vein) in the leg 26 thereby
increasing the speed of blood and WSS in the accepting vein to the
desired level and for a period of time sufficient to cause a
persistent increase in the lumen diameter and overall diameter of
the accepting greater saphenous vein 30. In the embodiment shown in
FIG. 3, the inflow conduit 16 is fluidly connected to a greater
saphenous vein 29 of the patient 20 via an anastomotic connection.
In some embodiments, the blood is pumped into the accepting vein
with a pulsatility that is reduced when compared with the
pulsatility of blood in a peripheral artery. For example, the mean
pulse pressure in the accepting vein adjacent to the connection
with the outflow conduit is <40 mmHg, <30 mmHg, <20 mmHg,
<10 mmHg, or preferably <5 mmHg with the pump operating. The
pumping of blood into the peripheral vein and the increase in blood
speed and WSS continues for a period of time sufficient to cause a
persistent increase in the overall diameter and lumen diameter of
the accepting greater saphenous vein segment 30 to facilitate
extraction and autotransplantation as part of a surgery to create a
cardiac or peripheral bypass graft, or other surgery that requires
autotransplantation of a portion of a patient's vein.
Referring to FIG. 4A, in another embodiment, an extracorporeal pump
114 is attached to two specialized catheters, an inflow catheter
55, and an outflow catheter 56 to form a catheter-pump assembly 13.
The pump 114 draws deoxygenated blood into the lumen of the inflow
catheter 55 from the donating vein 29 and then discharges the blood
from the outflow catheter 56 and into the lumen of the peripheral
accepting vein 30, thereby increasing the speed of blood and the
WSS in the peripheral accepting vein 30.
FIGS. 4A and 4B illustrate another embodiment of the system 10. The
pump-catheter assembly 13 is configured to increase the blood speed
and WSS in vein segment d. The inflow catheter 55 and the outflow
catheter 56 may optionally be joined in all or some portions (such
as with a double lumen catheter) and can be percutaneously inserted
into the lumen of the accepting peripheral vein 30, obviating the
need for an invasive surgical procedure. For this embodiment, a
portion of the catheter can be tunneled subcutaneously before
exiting the skin in order to reduce the risk of infection.
Extracorporeal portions of the catheters 119 and 120 and the
extracorporeal pump 114 can be affixed to the body, connected to a
power source, and operated in a manner that increases the speed of
the blood 34 and WSS in segment d of the accepting peripheral vein
30 for a period of time sufficient to cause a persistent increase
the overall diameter and lumen diameter of segment d of the
accepting peripheral vein 30. Once the desired amount of diameter
enlargement has occurred in segment d of the accepting peripheral
vein 30, the pump-catheter assembly 12 is removed and a surgical
procedure can be performed to create a hemodialysis access site or
bypass graft using at least a portion of the enlarged segment d of
the accepting peripheral vein 30, either at the same time or in a
subsequent operation.
Referring to FIGS. 5A and 5B, a system 10 to increase the overall
diameter of veins is illustrated as used for a patient 20. The
system 10 removes oxygenated arterial blood from a patient's
peripheral artery 221 and redirects that blood into the accepting
peripheral vein 30 and is configured and operated to increase the
blood speed and WSS in the accepting peripheral vein 30 for a
period of time sufficient to cause a persistent increase in the
diameter of the accepting peripheral vein 30 in, for example, an
arm 24 or a leg 26. An embodiment of a system 10 in which a pump
214 is implanted in the arm 24 is illustrated. The pump 214 has an
inlet 216 connected to an artery 221 in the arm 24 via anastomotic
connection. The pump 214 also has an outlet 218 connected to the
peripheral vein 30 via an anastomotic connection. The pump 214 is
controlled and powered by the control unit 58. In operation, the
pump 214 withdraws blood from the artery 221 and pumps the blood
into the peripheral vein 30. This embodiment can allow the
performance of a surgical procedure that avoids the need for
extended synthetic conduits and increases blood speed and WSS in
both the peripheral vein 30 and the peripheral artery 221 resulting
in, if operated for a sufficient period of time, simultaneous
dilation of the vein 30 and the artery 221. Specifically, the pump
214 is implanted in the forearm of the patient 20. Once the desired
amount of diameter enlargement has occurred in the accepting
peripheral vein 30, the pump 214 can be removed and a surgical
procedure can be performed to create a hemodialysis access site or
bypass graft using at least a portion the enlarged artery 221 or
vein 30, either at that time or during a subsequent operation.
In various embodiments, oxygenated arterial blood may be drawn from
a donating artery. Donating arteries may include, but are not
limited to, a radial artery, ulnar artery, interosseous artery,
brachial artery, anterior tibial artery, posterior tibial artery,
peroneal artery, popliteal artery, profunda artery, superficial
femoral artery, or femoral artery.
Referring to FIG. 6, a schematic of an embodiment of the system 10
is illustrated. The control unit 58 is connected to the pump 14 and
is configured to control the speed of the pump 14 and collect
information on the function of the pump 14. The control unit 58 may
be implanted in the patient 20, may remain external to the patient
20, or may have implanted and external portions. A power source is
embodied in a power unit 60 and is connected to the control unit 58
and the pump 14. The power unit 60 provides energy to the pump 14
and the control unit 58 for routine operation. The power unit 60
may be implanted in the patient 20, may remain external to the
patient 20, or may have implanted and external portions. The power
unit 60 may include a battery 61. The battery 61 is preferably
rechargeable and is recharged via a connector 69 to an AC source.
Such rechargeable batteries could also be recharged using lead
wires or via transcutaneous energy transmission. Optionally, the
connector 69 may deliver electrical power to the power unit 60
without the aid of the battery 61. It will be apparent to one of
ordinary skill in the art from this disclosure that the control
unit 58 can be configured to utilize alternative power-control
systems.
Sensors 66 and 67 may be incorporated into the synthetic conduits
17 and 18, the pump 14, or the control unit 58. The sensors 66 and
67 are connected to the control unit 58 via cable 68 or can
wirelessly communicate with the control unit 58. The sensors 66 and
67 can monitor blood flow, blood speed, intraluminal pressure, and
resistance to flow and may send signals to the control unit 58 to
alter pump speed. For example, as the peripheral vein 30 receiving
the pumped blood dilates, blood speed in the vein decreases, along
with resistance to blood flow 34 from the outflow conduit 18. In
order to maintain the desired blood speed and WSS, the pump speed
must be adjusted as the peripheral vein 30 dilates over time. The
sensors 66 and 67 may sense blood speed in the peripheral vein 30
or resistance to blood flow and then signal the control unit 58
which then increases the speed of the pump 14 accordingly. Thus,
the present invention advantageously provides a monitoring system,
constituted by the control unit 58 and sensors 66 and 67, to adjust
the pump speed to maintain the desired blood speed and WSS in the
accepting peripheral vein 30 as it dilates over time.
Alternatively, the control unit may rely on a measurement,
including an internal measurement of the electrical current to the
motor 44 as a basis for estimating blood flow, blood speed,
intraluminal pressure, or resistance to flow, thus obviating the
need for sensors 66 and 67. The control unit 58 may also include
manual controls to adjust pump speed or other pumping
parameters.
The control unit 58 is operatively connected to the pump-conduit
assembly 12. Specifically, the control unit 58 is operatively
connected to the pump 14 by one or more cables 62. Utilizing the
power unit 60, the control unit 58 preferably supplies pump motor
control current, such as pulse width modulated motor control
current to the pump 14 via cable 62. The control unit 58 can also
receive feedback or other signals from the pump 14. The control
unit 58 further includes a communication unit 64 that is utilized
to collect data and communicate the data, via telemetric
transmission, for example. Furthermore, the communication unit 64
is configured to receive instructions or data for reprogramming the
control unit 58. Therefore, the communication unit 64 is configured
to receive instructions or data for controlling the pump 14.
The present invention advantageously provides a monitoring system,
constituted by the control unit 58 and sensors 66 and 67, to adjust
the operation of the pump to maintain the desired blood speed and
WSS in the accepting peripheral vein 30 as it dilates over
time.
Preferably, the pump 14 is configured to provide a blood flow 34 in
a range from about 50-1500 mL/min, for example, and increase the
WSS in an accepting peripheral vein to a range of between 0.76 Pa
and 23 Pa, preferably to a range between 2.5 Pa and 7.5 Pa. The
pump 14 is configured to maintain the desired level of blood flow
and WSS in the accepting peripheral vein 30 for a period of about
7-84 days, for example, and preferably about 14-42 days, for
example. In certain situations where a large amount of vein
dilation is desired or where vein dilation occurs slowly, the pump
14 is configured to maintain the desired level of blood flow and
WSS in the accepting peripheral vein 30 for longer than 42
days.
The pump-conduit assembly 12 can be implanted on the right side of
the patient 20, or can be implanted on the left side, as need be.
The lengths of the conduits 16 and 18 can be adjusted for the
desired placement. Specifically for FIGS. 1B and 1C, the first end
46 of the inflow conduit 16 is fluidly connected to the location 29
in the right internal jugular vein 29 and the first end 52 of the
outflow conduit 18 is fluidly connected to the cephalic vein 30 in
the right forearm. Specifically for FIGS. 2B and 2C, the first end
46 of the inflow conduit 16 is fluidly connected to the location 29
in the superior vena cava 27 and the first end 52 of the outflow
conduit 18 is fluidly connected to the cephalic vein 30 in the
right forearm 24. After connection, pumping is started. That is,
the control unit 58 begins to operate the motor 44. The pump 14
pumps blood 34 through the outlet conduit 18 and into the
peripheral vein 30. The control unit 58 adjusts pumping over the
course of time by utilizing data provided by the sensors 66 and 67.
FIGS. 1-4 illustrate examples in which the system 10 pumps
deoxygenated blood. FIG. 5 illustrates an example in which the
system 10 pumps oxygenated blood. In some embodiments, the blood is
pumped into the accepting vein with a pulsatility that is reduced
when compared with the pulsatility of blood in a peripheral artery.
For example, the mean pulse pressure in the accepting vein is
<40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, or preferably
<5 mmHg with the pump operating and delivering blood into the
peripheral vein. In other embodiments, the blood is pumped into the
accepting vein with a pulsatility that is equal to or increased
when compared with the pulsatility of blood in a peripheral artery.
For these embodiments, the mean pulse pressure in the accepting
vein adjacent to the connection with the outflow conduit is >40
mmHg with the pump operating.
In one specific embodiment illustrated in FIGS. 1B and 1C, the
donating vein 29 is a jugular vein 21, preferentially an internal
jugular vein 21. The internal jugular vein 21 is particularly
useful as a donating vein 29 due to the absence of valves between
the internal jugular vein 21 and the right atrium 31, which would
allow the synthetic inflow conduit 16 to be able to draw a large
volume of deoxygenated blood per unit time. The inflow conduit 18
is fluidly connected to the internal jugular vein 21 of the patient
20. Deoxygenated blood is drawn from the internal jugular vein 21
and pumped into the peripheral accepting vein 30 in the arm 24 or
leg 26 resulting in an increase in the speed of blood 34 and WSS in
the peripheral accepting vein. In some embodiments, the blood is
pumped into the accepting vein with a pulsatility that is reduced
when compared with the pulsatility of blood in a peripheral artery.
For example, the mean pulse pressure in the accepting vein adjacent
to the connection with the outflow conduit is <40 mmHg, <30
mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg with the
pump operating.
As noted previously, FIG. 5B illustrates an example in which the
system 10 draws oxygenated blood. The inflow conduit 216 is fluidly
connected to the radial artery 221 of the patient 20 and the
outflow conduit 218 is fluidly connected to the cephalic vein, both
using an anastomotic connection. Thus, oxygenated blood is drawn
from the radial artery 221 and pumped into the cephalic vein 30 in
the arm 24 in a manner that results in an increased blood speed and
WSS in the cephalic vein for a sufficient period of time to cause a
persistent increase in the overall diameter and lumen diameter of
the accepting peripheral vein. In some embodiments, the blood is
pumped into the accepting vein with a pulsatility that is reduced
when compared with the pulsatility of blood in a peripheral artery.
For example, the mean pulse pressure in the accepting vein adjacent
to the connection with the outflow conduit is <40 mmHg, <30
mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg with the
pump operating and delivering blood into the peripheral accepting
vein.
Referring to FIGS. 7-9, various embodiments of the method 100
increase the overall diameter and the lumen diameter of the
peripheral vein 30. As shown in FIG. 7, a physician or surgeon
performs a procedure to access a vein or artery and connects a pump
to establish fluid communication with a vein carrying deoxygenated
blood at step 101. At step 102, the pump is connected to a
peripheral vein. In this embodiment, the pump-conduit assembly 12
is preferably implanted in the neck, chest and the arm 24 of the
patient 20. In another embodiment, wherein the peripheral vein 30
is the saphenous vein 36, the pump-conduit assembly 12 is implanted
in the leg 26. In one example, the physician fluidly connects the
first end 46 of the pump-conduit assembly 12 to the donating vein
29 and the second end of the pump-conduit assembly 12 to the
peripheral accepting vein 30, utilizing a tunneling procedure (as
necessary) to connect the two locations subcutaneously. At step
103, the deoxygenated blood is pumped into the peripheral accepting
vein. At step 104, the pumping continues for a period of time,
while the physician waits for the peripheral accepting vein to
dilate. In one embodiment, after the pump is turned on to start the
pumping of deoxygenated blood, the skin incisions are closed, as
necessary.
In another embodiment, portions of the synthetic conduits 16 and 18
and/or the pump 14 are extracorporeally located. In this
embodiment, the pump 14 is then started and controlled via the
control unit 58 to pump the deoxygenated blood through the
pump-conduit assembly 12 and into the peripheral accepting vein 30
in a manner that increases the blood speed and WSS in the
peripheral vein 30. The pumping process is monitored periodically
and the control unit 58 is used to adjust the pump 14, in response
to changes in the peripheral accepting vein 30. With periodic
adjustments, as necessary, the pump continues to operate for an
amount of time sufficient to result in the persistent dilation of
the overall diameter and lumen diameter of the peripheral vein 30.
In a subsequent procedure, the pump-conduit assembly 12 is
disconnected and removed at step 105. At step 106, the persistently
dilated peripheral vein 30 is used to create an AVF, AVG, or bypass
graft.
In another embodiment of the method 100, as shown in FIG. 8, the
physician or surgeon inserts one or more catheter portions 50 of
the pump-catheter assembly into the venous system and positions
them in a donating vessel and a peripheral vein 30 at step 107. At
step 108, the pump is operated to pump deoxygenated blood into the
deoxygenated blood. The physician then waits for the peripheral
vessel to dilate at step 109. The pump-catheter assembly is removed
and the persistently dilated vein is used to create an AVF, AVG, or
bypass graft, at steps 110 and 111, respectively.
FIG. 9 shows, yet another embodiment of the method 100. At step
112, a physician or surgeon performs a procedure to access a vein
and connects a pump to establish fluid communication with a
peripheral vein. At step 113, the pump is connected to a peripheral
artery. The pump is operated, at step 114 to pump oxygenated blood
from the peripheral artery to the peripheral vein. At step 115, the
pumping continues for a period of time, while the physician waits
for the peripheral vein dilate. At step 116, the pump is removed
and at step 117, the persistently dilated vein is used to create an
AVF, AVG, or bypass graft.
In various embodiments, the method 100 and/or the system 10 may be
used to in periodic and/or intermittent sessions, as opposed to
continuous treatment. Typically, hemodialysis treatments that may
last from 3 to 5 hours are given in a dialysis facility up to 3
times a week. Therefore, various embodiments of the system 10 and
method 100 may be used to provide blood pumping treatments on a
similar schedule over a 4 to 6 week period. The treatments may be
performed in any suitable location, including in an outpatient
setting.
In one embodiment, the blood pumping treatment is done
intermittently in conjunction with hemodialysis treatments. In this
embodiment, a low-flow pump, a standard in-dwelling hemodialysis
catheter functioning as an inflow catheter, and a minimally
traumatic needle or catheter placed in the peripheral vein to
function as an outflow catheter may be used. A number of continuous
flow blood pumps operated from a bedside console [e.g.
catheter-based VADs and pediatric cardiopulmonary bypass (CPB) or
extracorporeal membrane oxygenation (ECMO) pumps] may be easily
adapted for use with the method 100.
In various embodiments where the blood pumping occurs through
periodic pumping sessions, the access to the blood vessels may also
occur through one or more ports or surgically created access sites.
By way of example and not limitation, the access may be achieved
through a needle, a peripherally inserted central catheter, a
tunneled catheter, a non-tunneled catheter, and/or a subcutaneous
implantable port.
In another embodiment of the system 10, a low-flow pump is used to
increase WSS and blood speed in a blood vessel. The low-flow pump
has an inlet conduit fluidly connected to a blood vessel and an
outlet conduit fluidly connected to a vein pumps blood from the
blood vessel to the vein for a period between about 7 days and 84
day. The low-flow pump pumps blood such that the wall shear stress
of the vein ranges between about 0.076 Pa to about 23 Pa. The
low-flow pump also includes an adjustment device. The adjustment
device may be in communication with a software-based automatic
adjustment system or the adjustment device may have manual
controls. The inlet conduit and the outlet conduit may range in
length from about 10 centimeters to about 107 centimeters.
The present invention also relates to a method of assembling and
operating a blood pump system, including various embodiments of the
pump-conduit system 10. The method includes attaching a first
conduit in fluid communication with the pump-conduit system 10 to
an artery and attaching a second conduit in fluid communication
with the pump-conduit system to a vein. The pump-conduit system 10
is then activated to pump blood between the artery and the
vein.
In understanding the scope of the present invention, the term
"comprising" and its derivatives, as used herein, are intended to
be open ended terms that specify the presence of the stated
features, elements, components, groups, integers, and/or steps, but
do not exclude the presence of other unstated features, elements,
components, groups, integers and/or steps. The foregoing also
applies to words having similar meanings such as the terms,
"including", "having", and their derivatives. The terms of degree
such as "substantially", "about" and "approximate" as used herein
mean a reasonable amount of deviation of the modified term such
that the end result is not significantly changed. For example,
these terms can be construed as including a deviation of at least
.+-.5% of the modified term if this deviation would not negate the
meaning of the word it modifies.
While only selected embodiments have been chosen to illustrate the
present invention, it will be apparent to those skilled in the art
from this disclosure that various changes and modifications can be
made herein without departing from the scope of the invention as
defined in the appended claims. For example, the size, shape,
location, or orientation of the various components can be changed
as needed and/or desired. Components that are shown directly
connected or contacting each other can have intermediate structures
disposed between them. The functions of one element can be
performed by two, and vice versa. The structures and functions of
one embodiment can be adopted in another embodiment. It is not
necessary for all advantages to be present in a particular
embodiment at the same time. Every feature that is unique from the
prior art, alone or in combination with other features, also should
be considered a separate description of further inventions by the
applicant, including the structural and/or functional concepts
embodied by such features. Thus, the foregoing descriptions of the
embodiments according to the present invention are provided for
illustration only, and not for limiting the invention as defined by
the appended claims and their equivalents.
* * * * *